This project focuses on the role of free radicals in Alzheimers disease (AD), with special emphasis on the accurate measurement of the effect of acetyl-L-carnitine (ALC) and other potential drugs on OH formation. The primary analytical method will be electron paramagnetic resonance (EPR) spectroscopy. This project is based on the hypothesis, developed in the laboratory of Dr. Davis Parker, that iron coordination by ALC effects the production of OH radicals, and that AD involves, either as cause or effect, damage to cytochrome c oxidase. To test these hypotheses we propose to characterize the complexation of iron by ALC and other drugs, determine the effect of ALC and other drugs on the iron-catalyzed production of OH, and characterize the cytochrome c oxidase from AD patients compared with that from normal donors. Our preliminary results show that ALC does complex iron, and that we can measure that complexation accurately. We also have demonstrated our ability to spin-trap OH and to measure the EPR spectrum of cytochrome c oxi se. This project will be tightly coupled to the other projects in this NCDDG-AD proposal, especially the project in Dr. Parker's laboratory, where the biological samples will be prepared for our studies.